Dietary fat and protein have both been highly correlated with colon cancer incidence. However, few studies have examined the role of protein in colon carcinogenesis using well-defined and controlled nutritional procedures. An objective of this proposal is to determine how the dietary concentrations, protein and fat, interact to influence colon cancer in rats. Semipurified diets (AIN) (3 x 3 factorial design) varying in corn oil (10, 20, or 40% of calories) and protein (8, 16, 33% of calories) will be fed. The percent of vitamins, minerals, and fiber will be adjusted to maintain a constant ratio with respect to calories. The main effects of dietary protein and fat as well as their interactions on MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) induced colon carcinogenesis will be determined. Two experiments have been designed such that the effects of diet on the initiation and promotion stages of colon carcinogenesis will be determined independently. A third study will examine the interaction of two biologically active constituents of colon contents which may mediate the enhancement of carcinogenesis by diet. There is evidence that bile acids, which are increased by high fat diets, promote colon carcinogenesis. Ammonia, which is a by-product of protein metabolism, may be another factor which influences the development of colon tumors. A 3 x 2 factorial experiment will examine the effects of 3 levels of ammonia and 2 levels of chenodeoxycholic acid (CDA) on the promotion of MNNG colon carcinogenesis. The main effects as well as the interactions of ammonia and CDA will be determined. This study will quantitate the relative effects of ammonia compared to a known promoter, CDA.